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黏膜相关恒定T细胞对维生素B前体和副产物的识别

Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells.

作者信息

Eckle Sidonia B G, Corbett Alexandra J, Keller Andrew N, Chen Zhenjun, Godfrey Dale I, Liu Ligong, Mak Jeffrey Y W, Fairlie David P, Rossjohn Jamie, McCluskey James

机构信息

From the Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, and.

the Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.

出版信息

J Biol Chem. 2015 Dec 18;290(51):30204-11. doi: 10.1074/jbc.R115.685990. Epub 2015 Oct 14.

DOI:10.1074/jbc.R115.685990
PMID:26468291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4683245/
Abstract

Vitamin B2 (riboflavin) is essential for metabolic functions and is synthesized by many bacteria, yeast, and plants, but not by mammals and other animals, which must acquire it from the diet. In mammals, modified pyrimidine intermediates from the microbial biosynthesis of riboflavin are recognized as signature biomarkers of microbial infection. This recognition occurs by specialized lymphocytes known as mucosal associated invariant T (MAIT) cells. The major histocompatibility class I-like antigen-presenting molecule, MR1, captures these pyrimidine intermediates, but only after their condensation with small molecules derived from glycolysis and other metabolic pathways to form short-lived antigens. The resulting MR1-Ag complexes are recognized by MAIT cell antigen receptors (αβ T cell receptors (TCRs)), and the subsequent MAIT cell immune responses are thought to protect the host from pathogens at mucosal surfaces. Here, we review our understanding of how these novel antigens are generated and discuss their interactions with MR1 and MAIT TCRs.

摘要

维生素B2(核黄素)对代谢功能至关重要,可由许多细菌、酵母和植物合成,但哺乳动物和其他动物无法合成,它们必须从饮食中获取。在哺乳动物中,微生物合成核黄素产生的修饰嘧啶中间体被认为是微生物感染的标志性生物标志物。这种识别是由称为黏膜相关恒定T(MAIT)细胞的特殊淋巴细胞进行的。主要组织相容性复合体I类样抗原呈递分子MR1捕获这些嘧啶中间体,但只有在它们与糖酵解和其他代谢途径产生的小分子缩合形成短寿命抗原之后。由此产生的MR1-抗原复合物被MAIT细胞抗原受体(αβT细胞受体(TCR))识别,随后的MAIT细胞免疫反应被认为可保护宿主免受黏膜表面病原体的侵害。在这里,我们回顾了我们对这些新型抗原如何产生的理解,并讨论了它们与MR1和MAIT TCR的相互作用。

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本文引用的文献

1
Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers.使用MR1四聚体鉴定表型和功能异质性的小鼠黏膜相关恒定T细胞。
J Exp Med. 2015 Jun 29;212(7):1095-108. doi: 10.1084/jem.20142110. Epub 2015 Jun 22.
2
Functional Heterogeneity and Antimycobacterial Effects of Mouse Mucosal-Associated Invariant T Cells Specific for Riboflavin Metabolites.对核黄素代谢产物具有特异性的小鼠黏膜相关恒定T细胞的功能异质性及抗分枝杆菌作用
J Immunol. 2015 Jul 15;195(2):587-601. doi: 10.4049/jimmunol.1402545. Epub 2015 Jun 10.
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In Vitro and In Vivo Analysis of the Gram-Negative Bacteria-Derived Riboflavin Precursor Derivatives Activating Mouse MAIT Cells.革兰氏阴性菌衍生的核黄素前体衍生物激活小鼠黏膜相关恒定T细胞的体外和体内分析
J Immunol. 2015 May 15;194(10):4641-9. doi: 10.4049/jimmunol.1403224. Epub 2015 Apr 13.
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T cell antigen receptor recognition of antigen-presenting molecules.T 细胞抗原受体识别抗原呈递分子。
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A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells.黏膜相关不变 T 细胞 T 细胞受体异质性的分子基础。
J Exp Med. 2014 Jul 28;211(8):1585-600. doi: 10.1084/jem.20140484. Epub 2014 Jul 21.
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MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage.MR1 限制性 MAIT 细胞通过独特的 T 细胞受体使用表现出配体识别和病原体选择性。
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Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire.平行的 MAIT 细胞 T 细胞克隆和深度测序揭示了稳定的寡克隆 TCRβ库。
Nat Commun. 2014 May 15;5:3866. doi: 10.1038/ncomms4866.
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Human lung epithelial cells contain Mycobacterium tuberculosis in a late endosomal vacuole and are efficiently recognized by CD8⁺ T cells.人肺上皮细胞在晚期内体空泡中含有结核分枝杆菌,并能被CD8⁺T细胞有效识别。
PLoS One. 2014 May 14;9(5):e97515. doi: 10.1371/journal.pone.0097515. eCollection 2014.
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T-cell activation by transitory neo-antigens derived from distinct microbial pathways.T 细胞通过源自不同微生物途径的短暂新抗原激活。
Nature. 2014 May 15;509(7500):361-5. doi: 10.1038/nature13160. Epub 2014 Apr 2.
10
MAITs, MR1 and vitamin B metabolites.MAIT 细胞、MR1 及维生素 B 代谢物。
Curr Opin Immunol. 2014 Feb;26:7-13. doi: 10.1016/j.coi.2013.09.007. Epub 2013 Oct 18.